Prospective Effectiveness and Safety Study of Cladribine in Participants Who Change First-line DMD Treatments for Multiple Sclerosis (CLAD CROSS)

ARR defined as the number of relapses per year. A relapse was defined as the appearance of new symptoms or the exacerbation of pre-existing symptoms that were attributed to Multiple Sclerosis (MS) and occurred over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. Baseline ARR was defined as the total number of relapses reported in the last 12 months prior to Cladribine treatment. ARR 12-months prior to End Of Study was calculated as the sum of the number of MS relapses reported at Visit 3 and Visit 4 divided by the number of days between Visit 4 date and Visit 2 date and multiplied by 365.25. For a change from baseline, 95 percent (%) Confidence Interval (CI) for the difference were presented together with summary statistics. These CIs were included as a descriptive measure of effect.

ARR defined as the number of relapses per year. A relapse was defined as the appearance of new symptoms or the exacerbation of pre-existing symptoms that were attributed to MS and occurred over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. ARR 12-months after start of Cladribine was calculated as the sum of the number of MS relapses reported at Visit 1 and Visit 2 divided by the number of days between Visit 2 date and Cladribine start date and multiplied by 365.25.For a change from baseline, 95% CIs for the difference were presented together with summary statistics. These CIs were included as a descriptive measure of effect.

EDSS assessed disability in 8 functional systems. It was a scale based on a standardized EDSS neurological examination, which comprised optic, brain stem, pyramidal, cerebellar, sensory, and cerebral functions, as well as walking ability. An overall score ranged from 0 (normal) to 10 (death due to MS) was calculated. Progression on EDSS was defined as at least a 1-point increase in the score or an increase of at least 1.5 points if the baseline EDSS score was 0.

Disability progression was assessed if at least one assessment (EDSS, T25FW or 9HPT) was available. As per definition, disability progression was derived as "Yes" if at least one of the below cases occured: 1. Visit 4 EDSS is greater than (>=) equal to (≥) 1 point >= Visit 3 EDSS if Visit 3 EDSS is > 0; 2. Visit 4 EDSS is 1.5 or > when Visit 3 EDSS is 0; 3. 20% increase in the T25FW score (average of the two trials) from Visit 3 to Visit 4; 4. 20% increase in the 9HPT score (The two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged) from Visit 3 to Visit 4. If none of those cases occurred, disability progression will be set to "No". The percentage of participants with 6-month disability progression at the EOS was presented including associated 95% Clopper Pearson exact intervals.

EDSS assessed disability in 8 functional systems. It was a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory & cerebral functions, as well as walking ability. An overall score ranged from 0 (normal) to 10 (death due to MS) was calculated. Improvement on EDSS was defined as a decrease in EDSS by at least 1 point (1.5 points if baseline EDSS was 1.5).

Disability improvement was assessed if at least one assessment (EDSS, T25FW or 9HPT) was available. As per definition, disability improvement was derived as "Yes" if at least one of the below cases occur:1. Visit 4 EDSS is ≥1 point smaller than Visit 3 EDSS if Visit 3 EDSS is greater than 1.5;2. Visit 4 EDSS is 0 when Visit 3 EDSS is 1.5;3. 20% decrease in the T25FW score (average of the two trials) from Visit 3 to Visit 4;4. 20% decrease in the 9HPT score (The two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged) from Visit 3 to Visit 4. If none of those cases occurred, disability improvement was set to "No". The percentage of participants with 6-month disability improvement at the end of study was presented including associated 95% Clopper Pearson exact intervals.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.

MSIS-29 was a 29-item self-report measure with 20 items related to physical scale and 9 items with psychological scale. All items have 5 options:1-not at all to 5-extremely. Each of2 scales are scored by summing responses across items, converting to 0-100 scale where 100 indicates great impact of disease on daily function (worse health). Physical impact score computed by summing items 1-20 inclusive (observed score). This score was then transformed to a score on a scale of 0-100 using the formula:[100 multiplied by(observed score minus(-)20)] divided by(100-20). The psychological impact score was computed by summing items number21-29 inclusive(observed score). This score was then transformed to score on scale of 0-100 using the formula:[100 multiplied by(observed score minus 9)]divided by(45-9). Total score range ranges from 0-100, lower total score shows less psychological/physical-related impact while a higher total score indicated greater psychological/physical-related impact.

Quality of Life was measured using the EQ-5D-3L questionnaire. The EQ-5D-3L asks participants to rate the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D-5L VAS was used to record a participants rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 =worst imaginable health state and 100 = best imaginable health state.

TSQM version 1.4 was a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions:12-14). Global Satisfaction- Question 12 scored as 1 (not at all confident) to 5 (extremely confident); question 13 scored as 1 (not at all certain) to 5 (extremely certain); and question 14 scored as 1 (extremely dissatisfied) to 7 (extremely satisfied). The scores of the domain were added together and an algorithm was used to create a score of 0 to 100. Higher scores indicated greater satisfaction.

According to the World Health Organization (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Adherence to treatment, calculated as 100 × Taken tablets/Prescribed tablets